The original aims of the proposed research were to investigate the roles which certain therapeutic modalities used to treat hypercholesterolemia in human beings influence the development of gallstone disease (e.g., clofibrate, cholestyramine, and polyunsaturated fatty acids in the diet). To this list has now been added oral contraceptives. The original animal model chosen for these studies was the squirrel monkey (Saimiri sciureus), in which gallstone formation approaches 100% when the animals are fed diets high in polyunsaturates. Studies on bile acid kinetics and pool sizes have indicated that these animals do indeed have smaller pools of bile acids than those consuming more saturated fats. A pilot study has been done showing that clofibrate will produce a decrease in plasma concentration, although bile samples are not yet analyzed. We have found that squirrel monkeys have certain constraints for the types of studies we propose. Their small size (600-800 grams) makes surgical manipulation both hazardous and difficult. It is, in addition, virtually impossible to obtain replacement animals for our experiments. We are fortunate in having investigated cholelithiasis in the much larger (5-6 kg) African green monkey (Cercopithecus aethiops) during the past year. They are also predisposed to gallstone formation, and show the same sensitivity to dietary fat. The nature of the plasma lipoproteins show differences under the influence of saturated or unsaturated fats, a phenomenon which we are actively investigating. We have produced surgical devices into two such animals and demonstrated that clean bile samples can be obtained by percutaneous puncture. Future experiments will follow our original aims, but will be extended to the study of interactions of dietary fat and oral contraceptive administration to this larger, more abundant, and probably more desirable species of monkey.